Drug General Information
Drug ID
D02VFB
Former ID
DIB016678
Drug Name
Miproxifene
Synonyms
Miproxifene phosphate; TAT-59
Drug Type
Small molecular drug
Indication Cancer [ICD9: 140-229; ICD10:C00-C96] Discontinued in Phase 3 [544738]
Company
Taiho Pharmaceutical Co Ltd
Structure
Download
2D MOL

3D MOL

Formula
C29H35NO2
Canonical SMILES
P(=O)(Oc1ccc(/C(=C(/c2ccc(cc2)C(C)C)\CC)/c2ccc(cc2)OCCN<br />(C)C)cc1)(O)O
CAS Number
CAS 115767-74-3
PubChem Compound ID
Target and Pathway
Target(s) Estrogen receptor Target Info Modulator [525689]
KEGG Pathway Estrogen signaling pathway
Prolactin signaling pathway
Thyroid hormone signaling pathway
Endocrine and other factor-regulated calcium reabsorption
Proteoglycans in cancer
NetPath Pathway FSH Signaling Pathway
EGFR1 Signaling Pathway
RANKL Signaling Pathway
Pathway Interaction Database Regulation of nuclear SMAD2/3 signaling
Signaling events mediated by HDAC Class II
Plasma membrane estrogen receptor signaling
LKB1 signaling events
Regulation of Telomerase
ATF-2 transcription factor network
AP-1 transcription factor network
FOXM1 transcription factor network
Validated nuclear estrogen receptor alpha network
Signaling mediated by p38-alpha and p38-beta
FOXA1 transcription factor network
Reactome Nuclear signaling by ERBB4
Nuclear Receptor transcription pathway
WikiPathways Estrogen signaling pathway
Nuclear Receptors Meta-Pathway
Estrogen Receptor Pathway
Signaling by ERBB4
JAK/STAT
Integrated Pancreatic Cancer Pathway
Leptin signaling pathway
miR-targeted genes in muscle cell - TarBase
Integrated Breast Cancer Pathway
Nuclear Receptors
References
Ref 544738Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000796)
Ref 525689Estrogen agonistic/antagonistic effects of miproxifene phosphate (TAT-59)Shibata J1, Toko T, Saito H, Lykkesfeldt AE, Fujioka A, Sato K, Hashimoto A, Wierzba K, Yamada Y.Author information1Hanno Research Center, Taiho Pharmaceutical Co., Ltd., 1-27 Misugidai, Hanno-City, Saitama, 357-8527, Japan.Erratum inCancer Chemother Pharmacol 2000;46(2):172. AbstractPURPOSE: We evaluated miproxifene phosphate (TAT-59) to elucidate its efficacy in antiestrogen therapy for breast cancer patients and to assess its tissue-selective estrogenic/antiestrogenic activity.METHODS: Using DP-TAT-59, a major and active metabolite of TAT-59, an in vitro cell growth inhibition test was performed. Antitumor activity was determined using TAT-59 against human tumor xenografts of the MCF-7 and the Br-10 cell lines andMCF-7-derived tamoxifen-resistant cell lines, R-27 and FST-1. The antitumor activity of DP-TAT-59 and DM-DP-TAT-59, major metabolites of TAT-59 found in human blood following a TAT-59 dose, was also examined after intravenous administration to experimental animals. The residual estrogenic activity of TAT-59, evaluated in terms of bone and lipid metabolism in ovariectomized rats, was then comparedwith that of tamoxifen.RESULTS: DP-TAT-59 significantly inhibited the proliferation of estrogen receptor-positive MCF-7 and T-47D tumor cells in the presence of 1 nM estradiol. TAT-59, given to mice bearing MCF-7 or Br-10 xenografts, at the dose level of 5 mg/kg, exerted a significant growth inhibitory effect that was stronger than that of tamoxifen. Moreover, R-27 and FST-1 tumors, which show a resistance to tamoxifen, responded strongly to TAT-59, suggesting that TAT-59 might be effective against tumors resistant to tamoxifen. The metabolites of TAT-59, DP-TAT-59 and DM-DP-TAT-59, showed similar antitumor activity. Both TAT-59 and tamoxifen suppressed the decrease in bone density and reduced the blood cholesterol levels in ovariectomized rats, suggesting that the estrogenic activity of TAT-59 is comparable to that of tamoxifen.CONCLUSIONS: On the basis of the above results, one may expect TAT-59 to become an effective drug in patients with tumors less sensitive to tamoxifen, while its estrogenic activity as determined by bone and lipid metabolism is similar to that of tamoxifen.PMID: 10663628 [PubMed - indexed for MEDLINE] ShareMeSH Terms, SubstancesMeSH TermsAnimalsAntineoplastic Agents, Hormonal/pharmacologyBreast Neoplasms/pathology*Cell Division/drug effectsDrug Screening Assays, AntitumorEstradiol/pharmacologyEstrogen Antagonists/pharmacology*FemaleHumansLipid MetabolismMiceMice, Inbred BALB CRatsRats, Sprague-DawleyReceptors, Estrogen/physiologyTamoxifen/analogs &amp; derivatives*Tamoxifen/pharmacologyTransplantation, HeterologousTumor Cells, Cultured/drug effectsSubstancesAntineoplastic Agents, HormonalEstrogen AntagonistsReceptors, EstrogenTamoxifenTAT 59EstradiolLinkOut - more resourcesOther Literature SourcesAccess more work from the authors - ResearchGateMedicalBreast Cancer - MedlinePlus Health InformationMiscellaneousESTRADIOL - Hazardous Substances Data BankTAMOXIFEN - Hazardous Substances Data BankPubMed Commons home Cancer Chemother Pharmacol. 2000;45(2):133-41.

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